| Structural highlights
Function
[ENT1_YEAST] Binds to membranes enriched in phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Required for endocytosis and localization of actin. Negatively regulated via phosphorylation.[1] [2] [3] [SLA2_YEAST] Required for cellular morphogenesis and polarization of the cortical cytoskeleton. It might act in concert with proteins such as CDC42 and CDC43 to limit the region of cortical patch formation to the cortex of the bud. Required for the accumulation and/or maintenance of plasma membrane H(+)-ATPase on the cell surface.
Publication Abstract from PubMed
Clathrin-mediated endocytosis, the main trafficking route from the plasma membrane to the cytoplasm, is critical to many fundamental cellular processes. Clathrin, coupled to the membrane by adaptor proteins, is thought to play a major structural role in endocytosis by self-assembling into a cage-like lattice around the forming vesicle. Although clathrin adaptors are essential for endocytosis, little is known about their structural role in this process. Here we show that the membrane-binding domains of two conserved clathrin adaptors, Sla2 and Ent1, co-assemble in a PI(4,5)P2-dependent manner to form organized lattices on membranes. We determined the structure of the co-assembled lattice by electron cryo-microscopy and designed mutations that specifically impair the lattice formation in vitro. We show that these mutations block endocytosis in vivo. We suggest that clathrin adaptors not only link the polymerized clathrin to the membrane but also form an oligomeric structure, which is essential for membrane remodeling during endocytosis.
An Organized Co-assembly of Clathrin Adaptors Is Essential for Endocytosis.,Skruzny M, Desfosses A, Prinz S, Dodonova SO, Gieras A, Uetrecht C, Jakobi AJ, Abella M, Hagen WJ, Schulz J, Meijers R, Rybin V, Briggs JA, Sachse C, Kaksonen M Dev Cell. 2015 Apr 20;33(2):150-62. doi: 10.1016/j.devcel.2015.02.023. PMID:25898165[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wendland B, Steece KE, Emr SD. Yeast epsins contain an essential N-terminal ENTH domain, bind clathrin and are required for endocytosis. EMBO J. 1999 Aug 16;18(16):4383-93. PMID:10449404 doi:10.1093/emboj/18.16.4383
- ↑ Watson HA, Cope MJ, Groen AC, Drubin DG, Wendland B. In vivo role for actin-regulating kinases in endocytosis and yeast epsin phosphorylation. Mol Biol Cell. 2001 Nov;12(11):3668-79. PMID:11694597
- ↑ Aguilar RC, Watson HA, Wendland B. The yeast Epsin Ent1 is recruited to membranes through multiple independent interactions. J Biol Chem. 2003 Mar 21;278(12):10737-43. Epub 2003 Jan 14. PMID:12529323 doi:http://dx.doi.org/10.1074/jbc.M211622200
- ↑ Skruzny M, Desfosses A, Prinz S, Dodonova SO, Gieras A, Uetrecht C, Jakobi AJ, Abella M, Hagen WJ, Schulz J, Meijers R, Rybin V, Briggs JA, Sachse C, Kaksonen M. An Organized Co-assembly of Clathrin Adaptors Is Essential for Endocytosis. Dev Cell. 2015 Apr 20;33(2):150-62. doi: 10.1016/j.devcel.2015.02.023. PMID:25898165 doi:http://dx.doi.org/10.1016/j.devcel.2015.02.023
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